Nanoparticle drug conjugates

a technology of nanoparticles and conjugates, applied in the field of nanoparticle conjugates, can solve the problems of poor interstitial permeation of liposomes

Active Publication Date: 2015-12-03
MEMORIAL SLOAN KETTERING CANCER CENT +1
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  • Abstract
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  • Claims
  • Application Information

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Benefits of technology

[0007]Presented herein are methods and compositions of nanoparticle drug conjugates (NDC), specifically silica-based nanoparticle platform with covalently attached drug molecules. A NDC has been demonstrated as a nanotherapeutic. The combination of size, molecular composition and che

Problems solved by technology

While interstitial permeation of liposomes may be poor due to their size, the fr

Method used

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Examples

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experimental examples

[0086]One example demonstrates exemplary synthesis of nanoparticle drug conjugates (e.g., silica-based nanoparticle platform with covalently attached drug molecules) and their characterization and preliminary biological evaluations.

[0087]With the commercial availability of des-morpholino-gefitinib (dMG), the desired aminopropyl-dMG (APdMG) was obtained through a nucleophilic substitution (e.g., in one step) of Boc protected amino propyl bromide, followed by acid deprotection (FIG. 1A, FIG. 10 (Scheme 1)). Additionally, the gefitinib analogue 2, which is described in further detail below, was readily obtained from 1 by coupling Fmoc-dPEG2-COOH, with a subsequent base deprotection step (FIG. 1A, FIG. 11 (Scheme 2)). To ensure that APdMG 1 and dPEG2APdMG 2 have retained activity against EGFR, H1650 cells were treated with the compounds and analyzed by western blot to assess phospho-Tyr168 levels in EGFR. The H1650 cells are a model human tumor-derived non-small-cell lung cancer (NSCLC)...

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Abstract

Described herein are nanoparticle drug conjugates (NDCs), which, in certain embodiments, comprise a non-toxic, multi-modality, clinically proven silica-based nanoparticle platform with covalently attached drug molecules/moieties. The nanoparticle drug conjugates (NDCs) demonstrate imaging capability and targeting ligands which efficiently clear through the kidneys. Furthermore, the conjugates incorporate therapeutic agents for cancer detection, prevention, and/or treatment.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority to and the benefit of, and incorporates herein by reference in their entireties, U.S. Provisional Patent Application Nos. 62 / 004,738 and 62 / 094,923, filed May 29, 2014 and Dec. 19, 2014, respectively.FIELD OF THE INVENTION[0002]This invention relates generally to nanoparticle conjugates for delivery of therapeutic agents (e.g., targeted drug release) for the detection, prevention, and treatment of cancer and other diseases.BACKGROUND OF THE INVENTION[0003]Nanotherapeutic delivery vehicles are typically macro- or supra-molecular multicomponent systems, ranging in size from 1-1,000 nm, that are either inherently therapeutic (e.g., no active pharmaceutical ingredient) or function as therapeutic delivery systems. To date, liposomal nanoparticles and biologics comprise a large proportion of the number of FDA-approved products or products in clinical trials used to treat a variety of cancer types, while a number...

Claims

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Application Information

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IPC IPC(8): A61K47/48A61K31/5377A61K31/506A61K49/00A61K51/06
CPCA61K47/48907A61K47/48884A61K49/0054A61K47/48246A61K31/506A61K31/5377A61K47/48338A61K51/06A61K49/0093A61K51/1244A61K47/65A61K47/60A61K47/6923A61P35/00A61K47/6929A61K47/64A61K47/6935
Inventor YOO, BARNEYBRADBURY, MICHELLEWIESNER, ULRICH
Owner MEMORIAL SLOAN KETTERING CANCER CENT
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